KDR (VEGFR2) somatic activating mutations occur in ~2–3% of NSCLC across histologies. KDR...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-KDR-NSCLC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-NSCLC |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Actionability Facts
| Biomarker | BIO-KDR |
|---|---|
| Variant | KDR (VEGFR2) somatic activating mutation in NSCLC (~2–3%); no KDR mutation-selected approved therapy; ramucirumab approved for NSCLC regardless of KDR status |
| Disease | DIS-NSCLC |
| ESCAT tier | IIIB |
| Recommended combinations | Pembrolizumab 200 mg q3w ± platinum chemotherapy — 1L NSCLC per PD-L1 and histology (KEYNOTE-189/407; not KDR-specific), Ramucirumab 10 mg/kg IV + docetaxel 75 mg/m² q3w — 2L NSCLC after platinum progression (REVEL; FDA 2014; approved regardless of KDR mutation status) |
| Evidence summary | KDR (VEGFR2) somatic activating mutations occur in ~2–3% of NSCLC across histologies. KDR is the primary signal transducer for VEGF-driven tumor angiogenesis; multiple approved anti-angiogenic agents target KDR/VEGFR2 (ramucirumab, cabozantinib, lenvatinib, sunitinib). Clinical evidence for KDR mutation-selected therapy in NSCLC: (1) Ramucirumab + docetaxel (REVEL, FDA 2014): approved 2L NSCLC (regardless of KDR status); ramucirumab is an anti-VEGFR2 antibody but approval is biomarker-unselected. (2) Bevacizumab + chemotherapy: VEGF-A targeted, not KDR-mutation selected; contraindicated in squamous histology (central tumor, hemorrhage risk). (3) Cabozantinib, lenvatinib: multi-RTK inhibitors with VEGFR2 activity; no KDR mutation- selected NSCLC approval; under investigation in basket trials. (4) Hypothesized predictive value: KDR activating mutation may confer intrinsic VEGFR2 activation independent of VEGF-A — theoretically higher VEGFR2 dependence. No prospective evidence that KDR mutation predicts better response to ramucirumab vs. KDR wild-type. Standard of care: chemoimmunother... |
Notes
ESCAT IIIB: KDR mutation in NSCLC is an investigational marker. Practical notes: (1) KDR mutation is detectable on comprehensive NGS panels; not in NCCN's required biomarker panel (EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, PD-L1, TMB for NSCLC). (2) Anti-angiogenic treatment decisions use VEGF/VEGFR2 protein expression (PD-L1 analogue reasoning) or histology (bevacizumab contraindicated in squamous), not KDR mutation. (3) For KDR-mutant NSCLC patients who have progressed on standard therapy, basket trial enrollment with a VEGFR2/multi-TKI arm is appropriate. (4) KDR mutation in other tumor types (e.g., angiosarcoma, renal cell carcinoma) may have different clinical significance — those contexts are outside this BMA scope.
Used By
No reverse references found in the YAML corpus.